Tin-117m is routinely produced for Serene at several reactor and cyclotron sites allowing for a range of products based on this isotope. Commercial products will be made at Theragenics Corporation that has expertise in manufacturing and international distribution of human radioactive devices.
Homogeneous tin-117m colloid has been fully developed with a product shelf-life of 2 weeks. cGMP production at IsoTherapeutics Group, LLC, has been established for animal and human clinical trials, and the facility has been audited and certified for GLP animal trials. Ongoing development of Serene’s tin-117m based radiopharmaceutical and medical devices is undertaken at this facility. Collaboration with academic centers for oncology and cardiovascular therapeutics is ongoing.
Osteoarthritis–Rats have been treated in non-GLP and GLP trials using a Lewis rat meniscal tear model of osteoarthritis. The non-GLP trial demonstrated safety, efficacy, and dosing information, and validated the joint retention of >99%. A larger GLP trial has been completed, which validated the results of the non-GLP trial.
Rheumatoid arthritis–Over 50 rats have been treated in trials using a Lewis rat collagen-induced model of rheumatoid arthritis. A small GLP trial has been completed which demonstrated safety.
Oncology—Successful tin-117m-DTPA animal toxicology, imaging and therapeutic trials were completed and were followed by the tin-DTPA human clinical trials for the treatment of pain from bone metastases from prostate, breast, lung and other malignancies.
Cardiovascular– Targeting agents for CD68 macrophages were developed and [tin-117m]-DOTA-annexin V was used in apoE genetically modified mice with induced vulnerable plaque. These studies indicated specific and highly localized bind to these CD68 macrophages. These studies proved that localized binding could safely result in in vivo imaging and therapy (reversal) of vulnerable plaque.
Canine osteoarthritis—A pilot safety trial of tin-117m colloid has been completed on five normal hounds. Data collection included histopathology, autoradiography, blood laboratory, joint fluid cytology, imaging, excretion radiation, and radiation field determination. These data demonstrated safety to subject dogs and caregivers, and joint retention >99.0%. A pivotal trial of tin-117m colloid has been completed at the University of Missouri College of Veterinary Medicine, Louisiana State University School of Veterinary Medicine, and Gulf Coast Veterinary Specialists in Houston, TX. This trial will determine the safety and effect of tin-117m colloid in client-owned dogs with naturally occurring osteoarthritis of the elbow joint. The trial includes collection and evaluation of blood, joint fluid cytology, imaging (MRI/CT/PET), excretion radiation, radiation field determination, lameness, owner assessment, investigator physical assessment, and force plate analysis.
Equine osteoarthritis—A proof of concept trial is being developed to treat naturally occurring osteoarthritis in horses. This trial will be conducted at a leading University of Veterinary Medicine in the United States.
Rheumatoid arthritis—A trial treating patients with rheumatoid arthritis, osteoarthritis and other arthritides involving synovitis with homogeneous tin-117m colloid is being developed in Canada, with commencement of enrollment anticipated in 2018. Additional multi-national trials are being designed for both developed and developing countries. Serene, LLC is collaborating with world leaders in nuclear medicine and international organizations interested in promoting isotope usage for diagnosing and treating medical conditions.
Oncology—More than 100 patients with end stage cancer and bone metastases from a variety of primary tumor types were enrolled in multiple international phase I/II trials using tin-117m DTPA. Results indicate that the product is safe, and that it was effective in reducing pain caused by the metastases, and in slowing the rate of growth of some of the tumors. Additional phase II/III trials are planned. Clinical trials in a variety of other oncologic indications have been designed, including other prostate therapeutics, GI cancers (GEPNET), localized cancer treatment devices and others.
Cardiovascular (carotid artery stenosis)—Patients with critical carotid artery stenosis vulnerable plaque who were undergoing carotid endarterectomy surgery were treated with tin-117m [DOTA] annexin V in Phase I/II trials. Results indicate that the product is safe, and that vulnerable plaque in coronary and carotid arteries and abdominal aortic aneurysms can be localized and imaged. Additional phase II/III trials are planned to examine therapeutic utility.